Instructions for Lorista H film-coated tablets 50 mg + 12.5 mg No. 90
Composition
active ingredients: losartan, hydrochlorothiazide;
1 film-coated tablet contains 50 mg of losartan potassium and 12.5 mg of hydrochlorothiazide;
excipients: pregelatinized starch, microcrystalline cellulose, lactose monohydrate, magnesium stearate, hypromellose, macrogol 4000, talc, quinoline yellow dye (E 104), titanium dioxide (E 171).
Dosage form
Film-coated tablets.
Main physicochemical properties: yellow, oval, slightly biconvex tablets, film-coated with a score on one side.
Pharmacotherapeutic group
Angiotensin II antagonists and diuretics. Losartan and diuretics.
ATX code C09D A01.
Pharmacological properties
Pharmacodynamics
Losartan and hydrochlorothiazide
It has been proven that the hypotensive effect of the components of the drug is additive, so the use of the components of the drug together reduces blood pressure to a greater extent than their administration separately. It is believed that the effect is the result of the concomitant action of both components. In addition, due to the diuretic effect, hydrochlorothiazide increases plasma renin activity and aldosterone secretion, reduces potassium concentration and increases plasma angiotensin II levels. Losartan administration blocks all physiological effects of angiotensin II and, due to inhibition of the effects of aldosterone, may attenuate the potassium loss associated with the use of the diuretic.
Losartan has a moderate and transient uricosuric effect. Hydrochlorothiazide slightly increases blood uric acid levels; the combination of losartan and hydrochlorothiazide attenuates diuretic-induced hyperuricemia.
The antihypertensive effect of the drug persists for 24 hours and is also maintained with prolonged use. In addition to a significant decrease in blood pressure, drug therapy had no clinically significant effect on heart rate.
The combination of losartan and hydrochlorothiazide is effective in lowering blood pressure in men and women, patients of Negroid and Caucasian races, middle-aged patients (< 65 years) and elderly patients (≥ 65 years), and is also effective in all stages of arterial hypertension.
Losartan
Losartan is a synthetic angiotensin II (type AT1) receptor antagonist for oral administration. Angiotensin II, a potent vasoconstrictor, is the primary active hormone of the renin-angiotensin system and an important determinant of the pathophysiology of hypertension. Angiotensin II binds to AT1 receptors, which are found in many tissues (e.g., vascular smooth muscle, adrenal glands, kidneys, and heart), and exerts several important biological effects, including vasoconstriction and aldosterone release. Angiotensin II also stimulates smooth muscle cell proliferation.
Losartan selectively blocks the AT1 receptor. In vitro and in vivo, losartan and its pharmacologically active metabolite, the carboxylic acid (E 3174), block all physiologically relevant effects of angiotensin II, regardless of the source or route of synthesis.
Losartan does not bind to or block receptors for other hormones and ion channels important for the regulation of cardiovascular activity. In addition, losartan does not affect the action of angiotensin-converting enzyme (kinase II), which is responsible for the breakdown of bradykinin. Therefore, undesirable reactions associated with increased bradykinin concentrations are not observed. When losartan is administered, the negative effect of angiotensin II on renin formation is inhibited, which leads to increased renin activity in the blood plasma. Increased renin activity leads to an increase in the level of angiotensin II in the blood plasma. Despite this, antihypertensive activity and a decrease in the level of aldosterone in the blood plasma are preserved, which indicates effective blockade of the angiotensin II receptor. After discontinuation of losartan therapy, plasma renin activity and the concentration of angiotensin II return to normal within three days.
Losartan and its major active metabolite bind more strongly to the AT1 receptor than to the AT2 receptor. The active metabolite is 10–40 times more potent than losartan on a volume percent basis.
Losartan does not affect autonomic reflexes and has no long-term effect on plasma norepinephrine levels.
Hydrochlorothiazide
Hydrochlorothiazide is a thiazide diuretic. The mechanism of antihypertensive action of thiazide diuretics is not fully understood. Thiazides act on the renal tubular mechanism of electrolyte reabsorption, thereby directly increasing the excretion of sodium and chloride in approximately equal amounts. The diuretic effect of hydrochlorothiazide reduces plasma volume, increases plasma renin activity, and increases aldosterone secretion, with subsequent increases in urinary potassium and bicarbonate loss and decreases in serum potassium. Perhaps through blockade of the renin-aldosterone system, concomitant administration of angiotensin II receptor antagonists contributes to the reversible potassium loss associated with thiazide diuretics.
After oral administration, the increase in diuresis begins within two hours, reaches a peak after 4 hours and lasts for 6–12 hours. The antihypertensive effect persists for no more than 24 hours.
Based on available epidemiological data, there is a cumulative dose-dependent relationship between the use of HT and the development of NMSC. In one study population, there were 71,533 cases of BCC and 8,629 cases of PCC, and in the control group, 1,430,833 and 172,462 cases, respectively. High-dose HT (>50,000 mg cumulative) was associated with an adjusted HR of 1.29 (95% CI: 1.23–1.35) for BCC and 3.98 (95% CI: 3.68–4.31) for PCC. A clear relationship between cumulative dose and response was observed for both BCC and PCC. Another study demonstrated a possible association between lip cancer (squamous cell carcinoma (SCC)) and HRT use: 633 cases of lip cancer were matched to 63,067 cases in the control group (a risk-adjusted sampling strategy was used). The relationship between cumulative dose and response was demonstrated by an adjusted odds ratio (OR) of 2.1 (95% CI: 1.7–2.6), increasing to an OR of 3.9 (3.0–4.9) at high doses (25,000 mg) and an OR of 7.7 (5.7–10.5) at the highest cumulative dose (100,000 mg) (see also section 4.4).
Pharmacokinetics
Absorption.
Losartan
After oral administration, losartan is well absorbed and undergoes first-pass metabolism to form one active carboxyl metabolite and other pharmacologically inactive metabolites. The systemic bioavailability of losartan is approximately 33%. The maximum concentration of losartan and its active metabolite is reached approximately one hour and 3-4 hours after administration, respectively. Food intake does not cause clinically significant deviations in the pharmacokinetic profile.
Distribution
Losartan
More than 99% of losartan and its active metabolite are bound to plasma proteins, mainly albumin. The volume of distribution of losartan is 34 L. In animal studies, losartan did not penetrate the blood-brain barrier to any great extent or at all.
Hydrochlorothiazide
Hydrochlorothiazide crosses the placental barrier, does not cross the blood-brain barrier; penetrates into breast milk.
Biotransformation
Losartan
Approximately 14% of an oral or intravenous dose of losartan is metabolized to its active metabolite. After oral or intravenous administration of radiolabeled (14C) losartan potassium, the plasma radioactivity is primarily due to losartan and its active metabolite. In 1% of subjects, losartan is only slightly converted to the active metabolite.
In addition to the active metabolite, inactive metabolites are formed, including two major metabolites formed by hydroxylation of the butyl chain and a minor metabolite, N-2 tetrazole glucuronide.
Breeding
Losartan
The plasma clearance of losartan and its active metabolite is approximately 600 ml/min and 50 ml/min, respectively. The renal clearance of losartan and its active metabolite is approximately 74 ml/min and 26 ml/min, respectively. After oral administration, 4% of the administered dose of losartan is excreted in the urine as unchanged drug and 6% as the active metabolite.
The pharmacokinetic properties of losartan and its active metabolite vary linearly with oral doses of losartan potassium up to 200 mg.
After oral administration, plasma concentrations of losartan and its active metabolite decline polyexponentially; the half-lives are approximately 2 hours and 6-9 hours, respectively. With a single daily dose of 100 mg, neither losartan nor its active metabolite accumulates significantly in plasma.
Both biliary and renal excretion play a role in the elimination of losartan and its active metabolites. Following an oral dose of radiolabeled (14C) losartan, approximately 35% of the radioactivity is recovered in the urine and 58% in the feces.
Hydrochlorothiazide
Hydrochlorothiazide is not metabolized but is rapidly excreted by the kidneys. Based on observations lasting at least 24 hours, the plasma half-life of hydrochlorothiazide was 5.6-14.8 hours. At least 61% of an oral dose is excreted unchanged within 24 hours.
Patient characteristics
Losartan and hydrochlorothiazide
Plasma concentrations of losartan and its active metabolite and absorption of hydrochlorothiazide in elderly hypertensive patients do not differ significantly from those in young hypertensive patients.
Losartan
After oral administration to patients with mild to moderate alcoholic cirrhosis, plasma concentrations of losartan and its active metabolites were 5 and 1.7 times higher, respectively, than in young volunteers.
Neither losartan nor its active metabolite can be removed by hemodialysis.
Indication
Treatment of arterial hypertension when losartan monotherapy or hydrochlorothiazide monotherapy is insufficient.
Contraindication
– Hypersensitivity to losartan, sulfonamide derivatives (such as hydrochlorothiazide) or to any of the excipients.
– Pregnant women or women planning to become pregnant (see section “Use during pregnancy or breastfeeding”).
– Severe renal failure (creatinine clearance < 30 ml/min).
– Severe liver failure, cholestasis, obstructive diseases of the biliary tract.
– Therapeutically resistant hypokalemia or hypercalcemia.
– Persistent hyponatremia.
– Symptomatic hyperuricemia/gout.
– Concomitant use with aliskiren in case of diabetes mellitus or renal impairment (GFR <60 ml/min/1.73 m2) (see sections “Special precautions for use” and “Interaction with other medicinal products and other types of interactions”).
Interaction with other medicinal products and other types of interactions
Losartan
Rifampicin and fluconazole have been reported to decrease the levels of the active metabolite. The clinical consequences of these interactions have not been evaluated.
As with other drugs that block angiotensin II receptors or their effects, concomitant use of potassium-sparing diuretics (e.g. spironolactone, triamterene, amiloride), potassium supplements, salt substitutes containing potassium, or other drugs that may increase serum potassium levels (e.g. drugs containing trimethoprim) may lead to increases in serum potassium. Concomitant use is not recommended.
As with other drugs that affect sodium excretion, lithium excretion may be reduced. Therefore, serum lithium levels should be carefully monitored when lithium salts are used concomitantly with angiotensin II receptor antagonists.
Non-steroidal anti-inflammatory drugs (acetylsalicylic acid at anti-inflammatory dosage regimens, selective COX-2 inhibitors) and non-selective NSAIDs may reduce the antihypertensive effect of angiotensin II receptor antagonists. Concomitant use of angiotensin II receptor antagonists or diuretics and NSAIDs may lead to deterioration of renal function, including possible acute renal failure, and to an increase in serum potassium, especially in patients with impaired renal function. This combination should be used with caution, especially in elderly patients. Adequate hydration and close monitoring of renal function should be ensured at the beginning of concomitant therapy and periodically thereafter.
In some patients with impaired renal function, concomitant use of angiotensin II receptor antagonists and agents that inhibit cyclooxygenase 2 may lead to further deterioration of renal function. These effects are usually reversible.
Hypotension as a primary or side effect is characteristic of tricyclic antidepressants, neuroleptics, baclofen, amifostine. Concomitant use of these drugs may increase the risk of hypotension.
Studies have shown that dual blockade of the RAAS with concomitant use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren increases the risk of adverse reactions such as hypotension, hyperkalemia and renal dysfunction, including acute renal failure, compared with the use of a single agent of the renin-angiotensin-aldosterone system (see sections "Contraindications", "Special instructions for use").
Hydrochlorothiazide
When used concomitantly, the following drugs may interact with thiazide diuretics.
Alcohol, barbiturates, narcotics, or antidepressants
Orthostatic hypotension may worsen.
Antidiabetic agents (oral agents and insulin)
Thiazides may affect glucose tolerance. Dosage adjustment of antidiabetic agents may be necessary. Metformin should be used with caution because of the risk of lactic acidosis due to possible renal dysfunction associated with hydrochlorothiazide.
Other antihypertensive agents
Additive effect.
Cholestyramine and colestipol resins
The absorption of hydrochlorothiazide is impaired in the presence of anion exchange resins. Single doses of cholestyramine or colestipol bind hydrochlorothiazide and reduce its absorption from the gastrointestinal tract by 85% and 43%, respectively.
Corticosteroids, ACTH
Electrolyte loss increases, especially the risk of hypokalemia.
Pressor amines (e.g. adrenaline)
A decrease in response to pressor amines is possible. The degree of this decrease is insignificant, therefore the use of these agents cannot be ruled out.
Non-depolarizing skeletal muscle relaxants (e.g. tubocurarine)
Possible increased response to muscle relaxants.
Lithium preparations
Diuretics reduce renal clearance of lithium and increase the risk of lithium toxicity; concomitant use is not recommended.
Drugs used to treat gout (probenecid, sulfinpyrazone, and allopurinol)
It may be necessary to adjust the dose of uric acid-reducing agents, since hydrochlorothiazide may increase the concentration of uric acid in the blood plasma. It may be necessary to increase the dose of probenecid or sulfinpyrazone. Concomitant use of thiazides may increase the likelihood of hypersensitivity reactions to allopurinol.
Anticholinergic drugs (e.g. atropine, biperiden)
Increased bioavailability of thiazide diuretics is associated with a decrease in gastrointestinal motility and gastric emptying rate.
Thiazides may reduce the renal excretion of cytotoxic agents and may enhance the myelosuppressive effect.
Salicylates
When using large doses of salicylates, hydrochlorothiazide may enhance the toxic effect of salicylates on the central nervous system.
Methyldopa
In some cases, hemolytic anemia has been observed with the combined use of hydrochlorothiazide and methyldopa.
Cyclosporine
When used simultaneously with cyclosporines, the risk of hyperuricemia and complications such as gout increases.
Cardiac glycosides
Thiazide-induced hypokalemia or hypomagnesemia contributes to the development of cardiac glycoside-induced arrhythmias.
Drugs affected by serum potassium disturbances
It is necessary to periodically monitor the concentration of potassium in the blood serum and conduct ECG monitoring when using the combined drug losartan/hydrochlorothiazide with drugs whose effect depends on the level of potassium in the blood plasma (such as cardiac glycosides and antiarrhythmics), as well as with drugs that cause ventricular tachycardia (torsades de pointes), including some antiarrhythmics, since hypokalemia contributes to the formation of ventricular tachycardia:
– class Ia antiarrhythmic drugs (e.g. quinidine, hydroquinidine, disopyramide);
– class III antiarrhythmic drugs (e.g. amiodarone, sotalol, dofetilide, ibutilide);
– some antipsychotics (e.g. thioridazine, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, sulpiride, sultopride, amisulpride, tiapride, pimozide, haloperidol, droperidol);
– other drugs (e.g. bepridil, cisapride, diphemanil, intravenous erythromycin, halofantrine, mizolastine, pentamidine, terfenadine, intravenous vincamine).
Calcium salts
Thiazide diuretics may increase serum calcium levels due to decreased excretion. If calcium-increasing drugs are required, serum calcium levels should be monitored regularly and the dose adjusted accordingly.
Impact on laboratory parameters
Due to their effect on calcium metabolism, thiazides may alter the results of parathyroid function tests.
Carbamazepine
Risk of symptomatic hyponatremia. Clinical monitoring of the patient and laboratory blood monitoring are necessary.
Contrast agents containing iodine
In case of diuretic-induced dehydration, there is an increased risk of acute renal failure, especially when high doses of iodine-containing drugs are administered. Patients should be rehydrated before their administration.
Amphotericin B (parenteral), corticosteroids, adrenocorticotropic hormone, laxatives, and glycyrrhizin (found in licorice).
Hydrochlorothiazide may exacerbate electrolyte imbalances, especially hypokalemia.
Application features
Losartan
Angioedema
Close monitoring should be established in patients with a history of angioedema (swelling of the face, lips, throat and/or tongue).
Arterial hypotension and volume depletion
In patients with volume and/or sodium depletion due to intensive diuretic therapy, salt restriction, diarrhea, or vomiting, symptomatic hypotension may occur, especially after the first dose and after dose increases. Such conditions require correction before administration of the drug or a reduction in the initial dose.
Disturbances of water and electrolyte balance
In patients with renal insufficiency, both with and without diabetes, electrolyte imbalances often occur that require correction. In clinical trials conducted in patients with type 2 diabetes and nephropathy, the incidence of hyperkalemia was higher in the losartan-treated group than in the placebo group. Therefore, regular monitoring of plasma potassium and creatinine clearance is necessary. Patients with heart failure and creatinine clearance between 30 and 50 ml/min require particularly careful monitoring. Concomitant use of potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes, or other medicinal products that may increase serum potassium (e.g., trimethoprim-containing medicinal products) is not recommended.
Liver dysfunction
Based on pharmacokinetic data indicating a significant increase in plasma concentrations of losartan in patients with cirrhosis, patients with a history of mild or moderate liver dysfunction should be given a reduced dose. There is no experience of therapeutic use of losartan in patients with severe hepatic impairment, and the drug is contraindicated in such patients.
Kidney dysfunction
As with other drugs that affect the renin-angiotensin-aldosterone system, increases in blood urea and serum creatinine have also been reported in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney; these changes in renal function may be reversible upon discontinuation of therapy. Losartan should be used with caution in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney. Kidney transplantation
There is no experience in using the drug in patients who have recently undergone kidney transplantation.
Primary hyperaldosteronism
Patients with primary aldosteronism generally do not respond to antihypertensive drugs that inhibit the renin-angiotensin system. Therefore, losartan tablets are not recommended for them.
Coronary heart disease and cerebrovascular disease
As with any other antihypertensive drug, a rapid decrease in blood pressure in patients with coronary heart disease and cerebrovascular disease may result in myocardial infarction or stroke.
Heart failure
In patients with heart failure, with or without renal impairment, there is a risk of severe hypotension and (very often acute) renal failure when using losartan, as with any other medicinal product that acts on the renin-angiotensin system.
Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy
As with other vasodilators, special caution should be exercised in patients with aortic or mitral valve stenosis or obstructive hypertrophic cardiomyopathy.
Ethnic features
Like angiotensin-converting enzyme inhibitors, losartan and other angiotensin antagonists are less effective in lowering blood pressure in black patients than in non-blacks, probably because of a higher frequency of low-renin states in the black hypertensive population.
Pregnancy
Angiotensin II receptor antagonists should not be initiated during pregnancy. Unless continued angiotensin II receptor antagonist therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with losartan should be stopped immediately, and, if possible, alternative therapy should be started.
Dual blockade of the renin-angiotensin-aldosterone system (RAAS)
The concomitant use of aliskiren and angiotensin II receptor antagonists or ACE inhibitors increases the risk of hypotension, hyperkalemia and renal dysfunction, including acute renal failure. Due to dual blockade of the renin-angiotensin-aldosterone system (RAAS), the concomitant use of aliskiren and angiotensin II receptor antagonists or ACE inhibitors is not recommended (see section 4.5). If dual RAAS blockade is necessary, renal function, electrolytes and blood pressure should be closely monitored. Angiotensin II receptor antagonists and ACE inhibitors should not be used concomitantly in patients with diabetes.
Hydrochlorothiazide
Arterial hypotension and electrolyte imbalance
As with other antihypertensive agents, symptomatic hypotension may occur in some patients when taking the drug. Patients should be observed for clinical signs of fluid or electrolyte imbalance (e.g., volume depletion, hyponatremia, hypochloremic alkalosis, hypomagnesemia, or hypokalemia), which may occur as a result of concomitant diarrhea or vomiting. In such patients, serum electrolyte levels should be determined periodically at appropriate intervals. In hot weather, hyponatremia of solution may occur in patients prone to edema.
Metabolic and endocrine effects
Thiazides may alter glucose tolerance. Dose adjustment of antidiabetic drugs, including insulin, may be necessary. Latent diabetes mellitus may become manifest during thiazide therapy.
Thiazides may reduce urinary calcium excretion and may cause a slight and transient increase in serum calcium. Marked hypercalcemia may be a sign of latent hyperparathyroidism. Thiazides should be discontinued before parathyroid function tests are performed.
Elevated cholesterol and triglyceride levels may also be associated with thiazide diuretic therapy.
Thiazide therapy may lead to hyperuricemia and/or gout in some patients. Since losartan reduces urinary uric acid, losartan in combination with hydrochlorothiazide reduces diuretic-induced hyperuricemia.
Thiazides should be used with caution in patients with impaired liver function or progressive liver disease, as they may cause intrahepatic cholestasis, and minor changes in fluid and electrolyte balance may precipitate hepatic coma. The drug is contraindicated in patients with severe hepatic impairment.
Non-melanoma skin cancer
Two epidemiological studies conducted from the Danish National Cancer Registry have shown an increased risk of non-melanoma skin cancer (NMSC) [basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)] with increasing cumulative dose of hydrochlorothiazide (HCTZ). The possible mechanism for the development of NMSC is the photosensitizing effect of HCTZ.
Patients taking GCS should be informed of the risk of developing NMSC, advised to regularly check their skin for new growths and to report any suspicious skin lesions immediately. In order to reduce the risk of developing skin cancer, patients should be advised of possible preventive measures, such as limiting exposure to sunlight and ultraviolet light and ensuring adequate skin protection in the event of such exposure. Suspicious skin lesions should be investigated as soon as possible, including biopsy with histological examination of the material. The use of GCS may also need to be reconsidered in patients with a history of NMSC (see also section “Adverse reactions”).
Choroidal effusion, acute myopia, and secondary angle-closure glaucoma
Sulfonamide drugs or sulfonamide derivatives may cause an idiosyncratic reaction resulting in choroidal effusion with visual field defect, transient myopia, and acute angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or eye pain and usually occur within hours to weeks of starting the drug. Untreated acute angle-closure glaucoma may lead to irreversible vision loss. Initial treatment includes discontinuation of the drug as soon as possible. If intraocular pressure remains uncontrolled, prompt medical or surgical treatment may be necessary. Risk factors for acute angle-closure glaucoma include a history of allergy to sulfonamides or penicillins.
Acute respiratory toxicity
Very rare cases of acute respiratory toxicity, including acute respiratory distress syndrome (ARDS), have been reported following the administration of hydrochlorothiazide. Pulmonary edema usually develops within minutes to hours after administration of hydrochlorothiazide. Initial symptoms include dyspnea, fever, worsening pulmonary function, and hypotension. If ARDS is suspected, Lorista® H should be discontinued and appropriate treatment should be initiated. Hydrochlorothiazide should not be given to patients who have previously experienced ARDS after taking hydrochlorothiazide.
Other states
Allergic reactions may occur in patients receiving thiazides, regardless of a history of allergic conditions or bronchial asthma. Relapses or worsening of systemic lupus erythematosus have been reported in patients receiving thiazides.
Special information about some of the excipients
This medicine contains lactose. Patients with rare hereditary forms of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Use during pregnancy or breastfeeding
Pregnancy
The drug is contraindicated for use in pregnant women or women planning to become pregnant. If pregnancy is confirmed during treatment with the drug, its use should be immediately discontinued and replaced with another drug approved for use in pregnant women.
Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy is inconclusive, but a small increased risk cannot be excluded. There are currently no controlled epidemiological data on the risk associated with angiotensin II receptor blockers, and a similar risk is possible for this class of drugs. Unless continued angiotensin II receptor blocker therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with angiotensin II receptor blockers should be stopped immediately, and, if possible, alternative therapy should be started.
It is known that the use of angiotensin II inhibitors during the second and third trimesters of pregnancy may cause fetotoxicity (decreased renal function, oligohydramnios with pulmonary hypoplasia, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalemia).
Should exposure to angiotensin II inhibitors have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended.
Infants whose mothers have taken angiotensin II inhibitors should be closely observed for hypotension, oliguria and hyperkalemia (see sections 4.3 and 4.4).
There is limited experience with the use of hydrochlorothiazide during pregnancy, especially during the first trimester. Animal studies are limited.
Hydrochlorothiazide crosses the placental barrier. Given the pharmacological mechanism of action of hydrochlorothiazide, its use during the 2nd and 3rd trimesters may impair the blood supply between the placenta and the fetus and cause jaundice, electrolyte imbalance and thrombocytopenia in the fetus and newborn.
Hydrochlorothiazide should not be used to treat gestational edema, as well as gestational hypertension or preeclampsia due to the risk of decreased plasma volume and uteroplacental hypoperfusion without a beneficial effect on the course of the disease.
Hydrochlorothiazide should not be used to treat hypertension in pregnant women unless no alternative treatment is available.
Breast-feeding
The use of the drug is not recommended due to the lack of sufficient data on the use during breastfeeding. The patient should be switched to alternative antihypertensive treatments which have an established safety profile for use during breastfeeding, especially in newborns or preterm infants.
Ability to influence reaction speed when driving vehicles or other mechanisms
No studies have been conducted on the effect of the drug on the ability to drive a car and work with other mechanisms.
However, when driving or operating machinery, dizziness or fatigue may occur when taking antihypertensive drugs, especially at the beginning of treatment or when the dose is increased.
Method of administration and doses
Lorista® H can be used with other antihypertensive agents.
The tablets of the drug should be swallowed with a glass of water.
The use of the drug does not depend on food intake.
The combination of losartan and hydrochlorothiazide should not be used as initial therapy. Whenever possible, it is advisable to titrate the doses of the components of the drug (losartan and hydrochlorothiazide).
If monotherapy with the components of the drug is not effective enough, the combined drug can be used directly.
Arterial hypertension
The usual starting and maintenance dose for most patients is 1 tablet of Lorista® H (50 mg/12.5 mg) once daily. In patients in whom 1 tablet of Lorista® H does not provide sufficient effect, the dose may be increased to 2 tablets once daily (in the morning).
The maximum hypotensive effect is achieved within 3–4 weeks of treatment. The maximum recommended dose is 2 tablets of Lorista® H once a day.
Use in patients with renal failure and patients on hemodialysis
For patients with moderate renal insufficiency (creatinine clearance 30–50 ml/min), no adjustment of the initial dose is required.
Losartan/hydrochlorothiazide tablets are not recommended for use in patients undergoing hemodialysis. Losartan/hydrochlorothiazide tablets are contraindicated in patients with severe renal impairment (creatinine clearance < 30 mL/min).
Use in patients with decreased intravascular volume of circulating fluid
Correction of volume and/or sodium depletion should be performed before initiating losartan/hydrochlorothiazide tablets.
Patient application
